Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Pembrolizumab

Albumin-Bound Paclitaxel

Olaparib

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

1. Neoadjuvant phase; Treatment 1: Pembrolizumab+ Paclitaxel + Carboplatin (Cycles 1-4) Treatment 2: Pembrolizumab + Olaparib (Cycles 1-4)
2. Definitive Surgery
3. Adjuvant phase; Pembrolizumab + Olaparib (1-9 cycles)

Note: each cycle = 3 weeks (Neoadjuvant Treatment 1 and 2, and Adjuvant Treatment)

200 mg fixed dose, IV, every 3 weeks (Q3W), on Days 1 of Cycles 1-4

80 mg/m2, IV, weekly, on Days 1, 8, 15 of Cycles 1-4

Area under the curve (AUC 1.5), intravenously (IV), weekly, on Days 1, 8, 15 of Cycles 1-4

Each subject will undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant treatment.

Definitive Surgery

Yuko Takahashi, MD., PhD.

Hironobu TAN, PhD.

Masaya Hattori, MD., PhD.

Kumiko Kida, MD., PhD.

This is a Phase II, single-arm, open label study to evaluate Olaparib plus Pembrolizumab following platinum-based chemotherapy plus Pembrolizumab as neoadjuvant therapy for germline BRCA (gBRCA) 1/2 mutated triple negative breast cancer (TNBC).

Pembrolizumab in combination with weekly paclitaxel and carboplatin (treatment 1) is followed by Pembrolizumab in combination with Olaparib (treatment 2) in neoadjuvant setting and Pembrolizumab in combination with Olaparib in adjuvant setting will be studied

Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer

Neoadjuvant and Adjuvant Olaparib Plus Pembrolizumab Following Platinum Based Chemotherapy Plus Pembrolizumab for Germline BRCA Mutated Triple Negative Breast Cancer (WJOG14020B/OPERETTA)

Pathological complete response rate (ypT0/TisypN0) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.

Residual Cancer Burden (RCB) 0/1 rate is defined as the proportion of subjects on evaluation from routine pathologic sections of the primary breast tumor and the regional lymph nodes after the completion of neoadjuvant therapy assessed by the local pathologist at the time of definitive surgery. Six variables are included in a calculation formula. The calculated RCB index value can also be categorized as one of four RCB classes (0 - 3). The calculation formula and detailed description can be found at a dedicated Web site: http://www.mdanderson.org/breastcancer_RCB.

Pathological complete response rate (ypT0/is) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen regardless of regional lymph nodes status following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.

The Proportion of Three Year-Overall Survival (3y-OS) is defined as the proportion of survival subjects without death due to any cause at 3 years from registration. Subjects without documented death at the time of the analysis will be censored at the date of the last follow-up.

The Proportion of Three-Year Distant Metastatic Free Survival (3y-DMFS) is defined as the proportion of survival subjects without distant metastatic disease at 3 years from registration. Subjects without documented distant metastatic disease at the time of the analysis will be censored at the date of the last follow-up.

The Proportion of Three-Year Disease Free Survival (3y-DFS) is defined as the proportion of survival subjects without metastatic disease and secondary malignancy at 3 years from registration. Subjects without documented metastatic disease and secondary malignancy at the time of the analysis will be censored at the date of the last follow-up.

Safety measurements are the incidence of, causality of, and outcome of AEs/SAEs; and changes in vital sign measurements and laboratory values.

Merck Sharp & Dohme LLC

Okayama University

Assistant professor, Endocrinological Center

Central Nervous System Depressants

Anesthetics

Anesthetics, Local

Patients in the control group will receive usual care. The surgical oncologist will perform the NSM and sentinel lymph node biopsy if indicated (active breast cancer or DCIS). We will submit a nipple core biopsy and a 1cm thick biopsy of immediately retro-areolar ductal tissue for permanent section pathology for control patients, and all patients will have the mastectomy specimen submitted for permanent section pathology. Under the same general anaesthesia, the plastic surgeon will perform the IBR (2-stage tissue expander to implant or 1-stage direct to implant). Patients who later have a positive nipple core and retro-areolar biopsy will have a discussion with the surgical oncologist regarding the need for revision breast surgery to excise the NAC, as is current practice.

Patients in the experimental group will have a nipple-delay intervention in addition to usual care. The nipple delay procedure will be performed by the plastic surgeon in the minor clinic procedure room under local anaesthetic 7 - 21 days prior definitive NSM with IBR. The skin flap will be elevated in the plane of the prophylactic mastectomy beneath the NAC. A nipple core biopsy and a 1cm thick biopsy of immediately subareolar ductal tissue will be submitted for permanent section pathology. This approach is consistent with the previous case series of nipple delay for NSM and approved by the multi-disciplinary breast cancer team at our institutions. Patients that have a positive nipple core or sub-areolar biopsy will have the NAC removed at time of definitive mastectomy.

The nipple delay surgery will be performed by the plastic surgeon as an outpatient procedure in the minor procedure room under local anaesthetic 7 - 21 days prior definitive NSM with IBR. The skin flap will be elevated in the plane of the prophylactic mastectomy beneath the NAC. A nipple core biopsy and a 1cm thick biopsy of immediately subareolar ductal tissue will be submitted for permanent section pathology. This approach is consistent with the previous case series of nipple delay for NSM and has been approved by the multi-disciplinary breast cancer team at our institutions. Patients that have a positive nipple core or sub-areolar biopsy will have the NAC removed at time of definitive mastectomy.

Nipple Delay surgery

The goal of nipple-sparing mastectomy (NSM) with immediate breast reconstruction is to reconstruct a breast mound with preservation a patient's natural skin envelope. Preservation of the nipple and areola complex during mastectomy and breast reconstruction is associated with improved quality of life and a better cosmetic result. However, this surgical technique relies on tenuous blood supply to maintain the nipple and areola. Therefore a certain proportion of women will actually lose their preserved nipple-areolar complex due to vascular insufficiency. Furthermore, some women may find out after a nipple-sparing mastectomy that cancer had invaded the nipple-areolar complex, and would require another operation to completely remove the cancer. Despite these devastating complications, there have been no controlled studies to investigate mechanisms to reduce the chance of their occurrence.

Our research study will use a pre-operative minor procedure to enhance blood flow to the nipple-areola complex prior to standard nipple sparing mastectomy among eligible women undergoing mastectomy for breast cancer or risk reduction. A secondary objective is to test how many women actually have active cancer in their nipple at the time of this minor surgical procedure, prior to standard NSM. The investigators hypothesize that our innovative and novel nipple-delay procedure will reduce the risk of loss of the nipple due to vascular insufficiency and may be of benefit to identify the small proportion of women with nipple-areola complex involvement, in order to optimize the ultimate cancer ablation.

For this study the investigators propose to undertake a Pilot RCT as the first step in the evaluation of a delay procedure prior to NSM, and the results will be used to determine the feasibility and inform the optimal design for a definitive RCT. This study question has the potential to set a new standard of care in the management of women seeking NSM for the management of their breast cancer.

The surgical management of breast cancer has evolved over the last few decades, with cancer extirpation becoming less aggressive in parallel with advances in breast reconstruction. Preservation of the nipple-areolar complex (NAC) at time of mastectomy (nipple-sparing mastectomy, NSM), represents a natural progression within reconstructive and surgical oncology to preserve maximum native skin as is oncologically feasible. NSM is associated with improved satisfaction, body image and psychological adjustment. NSM has received increased attention in the lay media, because the ability to preserve the entire breast envelope appeals to patients facing the decision to undergo mastectomy.

Clinician attention regarding NSM has focused on the oncologic implications of the residual breast tissue. Several systematic reviews of prospective and retrospective studies (level II to IV) have concluded that NSM does not impair overall or breast cancer specific survival outcomes compared to skin-sparing mastectomy. This has fostered the adoption of NSM within North America and Europe. The rate of occult NAC involvement ranges from 6 - 30%.

However, the intended purpose of NSM to preserve the NAC may be circumvented if a tenuous sub-dermal blood supply compromises NAC viability. Rates of NAC necrosis are variable, from 0% to nearly 50% of cases 5,6. Few studies explored strategies to prevent this potentially devastating complication. Recent case series employ the use of the surgical delay phenomenon to improve vascular supply and reduce NAC necrosis during NSM 9,10, however this strategy has not been directly compared with standard NSM.

There have been no controlled studies to investigate mechanisms to reduce the chance of potentially devestating complication of NAC necrosis or minimize the clinical impact of occult tumor involvement in the NAC. Because our study is a pilot feasibility study, we have 3 specific rationale to support our design using a pilot study first:

1. : Given lack of evidence to support impaired cancer outcomes, there has been greater interest in NSM within our breast cancer community. Prior to initiating a full trial, it is paramount to determine the extent to which the intervention can be provided as intended.
2. There are a number of well-described challenges to undertaking a RCT of a surgical intervention, and the extent to which women consent to participate, maintain randomized treatment allocation and adhere to study protocol will inform whether this study is feasible at a larger scale. It has not been determined whether candidates for NSM would accept an additional surgical procedure to reduce the risk of NAC necrosis. Lastly, there is the opportunity to identify and revise organization and protocols prior to execution within a full trial.
3. : Given there is wide variation in reported rates of NAC necrosis, it is important to determine the incidence of NAC necrosis within our institutions and use this information to generate and inform sample size calculation. The direction of benefit and preliminary estimates of the effect of the intervention will clarify the choice of primary and secondary outcomes and feasibility for a larger scale study.

The overarching hypothesis driving the main trial is that patients who are allocated to nipple-delay will have a lower rate of NAC necrosis. Additionally we hypothesize may be of benefit to identify the small proportion of women with nipple-areola complex involvement, in order to optimize the ultimate cancer ablation.

Aim 1: To assess treatment fidelity and acceptability to surgeons of the intervention Hypothesis: This pilot RCT will be acceptable to surgeons, and surgeons will adhere to the treatment group (surgical procedure) to which their patient is randomly allocated. Aim 2: To determine feasibility and acceptability to patients of randomization, treatment uptake and retention and data-collection Hypothesis: This pilot RCT will be feasible to implement and acceptable to patients, and the results will inform planning of the main study. Aim 3: To estimate the proportion of patients in the treatment and control groups that develop NAC necrosis (primary outcome) and a preliminary estimate of the effect of the intervention on NAC necrosis (primary outcome), occult cancer and intra-operative NAC perfusion (secondary outcomes). Hypothesis: This pilot study will provide important information regarding treatment effect estimate and variability (standard deviation) that will be used to guide the design and sample size calculation for the main trial. The overarching hypothesis driving the main trial is that patients who are allocated to nipple-delay will have a lower rate of NAC necrosis.

Pilot outcomes: Treatment fidelity and acceptability to surgeons: We will record the proportion of participants who received their randomly allocated treatment assignment to monitor participant adherence to treatment allocation. We will record reasons why any deviation from study protocol occurred (patient or surgeon-driven), and other organizational barriers to meeting usual care (ex: \> 21 days between nipple-delay and NSM for experimental-group patients). Feasibility and acceptability of randomization, treatment allocation and data-collection procedures: Patient recruitment and attrition rates will be recorded. We will measure the proportion of participants that generate complete primary and secondary outcome measurements and baseline questionnaires.

Trial outcomes:

Primary outcome: We will compare the proportion of patients in each group that develop NAC necrosis, defined as necrosis requiring local wound care with dressings or surgical debridement. The proportion of patients in each group that develop total (\> 75% of NAC) and partial (25 to 75% of NAC) NAC necrosis will be measured at 2 week and 4 weeks after the definitive NSM procedure by the treating plastic surgeon and surgical oncologist, respectively. We will take photographs to provide objective documentation.

Secondary outcomes:

1. The proportion of women in each group who require secondary NAC excision due to positive pathology review after NSM after the retro-areolar and nipple core biopsy during surgical delay (intervention group) or definitive NSM (control group).
2. To include an objective and immediate measure of NAC perfusion, we will compare the mean perfusion score of the NAC between groups using indocyanine green infusion and the SPY Imaging System (Lifecell Corp.) immediately after tissue expander or implant placement and skin closure during the NSM. We will use this as an objective measure of perfusion but will not influence clinical decision making with regards to NAC viability.

For the pilot, this study is significant to generate high-quality evidence-based data and to determine the feasibility to undertake and complete a full-scale RCT. The overarching study has the potential to influence clinical practice and is very contemporary in the management of patients undergoing mastectomy for breast cancer or risk reduction. If nipple-delay is effective in reducing the rate of NAC necrosis, then our proposed intervention has the potential to change clinical practice for surgeons who treat women with breast cancer or at high risk for development. Furthermore, the identification of occult malignancy within the NAC prior to planned NSM may contribute to improved cancer outcomes by not sparing the NAC at the time of mastectomy. We hypothesize a positive outcome would engender support within the breast cancer community to uptake an additional stage. Therefore, our proposed study can be used as a model to incorporate level I evidence into the plastic surgery research community, as well as provide robust data to support a change in clinical practice to improve patient outcomes among women undergoing NSM for breast cancer risk-reduction.

Nipple Delay Prior to Nipple Sparing Mastectomy: A Pilot RCT

We will compare the proportion of patients in each group that develop NAC necrosis, defined as necrosis requiring local wound care with dressings or surgical debridement. The proportion of patients in each group that develop total (\> 75% of NAC) and partial (25 to 75% of NAC) NAC necrosis will be measured at 2 week and 4 weeks after the definitive NSM procedure by the treating plastic surgeon and surgical oncologist, respectively. We will take photographs to provide objective documentation.

University Health Network, Toronto

Standard mammography

Standard mammography and tomosynthesis

cedric De Bazelaire, MD PHD

Matthieu Resche-Rigon, MD PHD

matthieu resche-rigon

Isabelle THOMASSIN- NAGGARA, Pr

Tomosynthesis is an innovative technique developed in digital mammography for obtaining a sectional image of the breast. Mammography has the main disadvantage of being an imaging projection that creates overlays, which eliminates tomosynthesis.

The objective of this study is to evaluate if the BI-RADS classification obtained by tomosynthesis with synthetic mammography is superior to that obtained by conventional mammography in terms of specificity while not inferior in terms of sensitivity.

Evaluation of Tomosynthesis for Characterization and the Management of Breast Lesions

EVALUATION DE LA TOMOSYNTHESE DANS LA CARACTERISATION ET LA PRISE EN CHARGE DES LESIONS MAMMAIRES : "ETOLE"

The primary evaluation parameter will be the classification error of tumors according to the BiRads scale obtained by mammography (BiRadsM) and by tomosynthesis (BiRadsT) according to the gold standard.

The visibility (presence or absence) of signs of poor prognosis criteria. We will compare the visibility of poor prognosis criteria seen on mammography + ultrasound and seen on tomosynthesis with synthetic mammography + ultrasound.

Needs for supplementary breast imaging exams and biopsies

The reproducibility of the interpretation of tomosynthesis will be assessed with differences of classifications BiRadsT observed between the two radiologists

Cumulative incidence of Breast cancer diagnosis among women with benign at after primary evaluation

Assistance Publique - Hôpitaux de Paris

Participants will receive two 50 mg capsules in the morning and two 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion is met.

Participants will receive eight 50 mg capsules in the morning and eight 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion is met.

Participants will receive capsules of olaparib orally as stated in arm description.

James Carmichael, BSc, MBChB, MD, FRCP

Andrew Tutt, PhD MRCP FRCR

The purpose of the study is to see if the drug KU-0059436 (olaparib) is effective and well tolerated in treating participants with measurable breast cancer gene (BRCA)1- or BRCA2-positive advanced breast cancer and for whom no curative therapeutic option exists.

This is a Phase II, open-label, non-comparative, international, multicenter study to assess the efficacy and safety of olaparib when given orally twice daily (bd) in participants with advanced BRCA1- or BRCA2- associated breast cancer. Two sequential participant cohorts will receive continuous oral olaparib in 28-day cycles. The first cohort will receive 400 mg bd and the second cohort will receive 100 mg bd.

Study to Assess The Efficacy and Safety of a PARP Inhibitor For The Treatment of BRCA-positive Advanced Breast Cancer

A Phase II, Open-label, Non-comparative, International, Multicentre Study to Assess the Efficacy and Safety of KU-0059436 Given Orally Twice Daily in Patients With Advanced BRCA1- or BRCA2-associated Breast Cancer.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

The ORR is the percentage of participants whose best tumor response is either complete response (CR) or partial response (PR), according to the RECIST v1.0 criteria. The CR is defined as disappearance of all target lesions (TLs). The PR is defined as at least a 30% decrease in the sum of longest diameters (LD) taking as reference the baseline sum of LD. Percentage of participants with ORR is reported.

Duration of response is defined as the date of progression per RECIST criteria - the date when CR or PR \[whichever is earliest\] is confirmed + 1. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Duration of response was analyzed for those participants who had OR.

The CBR is defined as the percentage of participants with a RECIST tumor response of confirmed CR, PR or stable disease (SD) for ≥ 8 weeks +/- 1 week visit window. The CR is defined as disappearance of all TLs. The PR is defined as at least a 30% decrease in the sum of LD taking as reference the baseline sum of LD. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum of LD since the treatment started.

The tumor size is defined as the sum of the longest diameters as measured among all target lesions. At each assessment, the percentage change in tumor size is defined as 100 × 1 - (sum of all target lesion diameters at visit/sum of all target lesion diameters at baseline).

PFS is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression. Those participants who were withdrawn from the study without disease progression were regarded as censored at their last evaluable RECIST assessment. Where participants had not progressed at the termination of the study, they were also regarded as censored at their last evaluable RECIST assessment. PFS was analyzed using Kaplan-Meier estimate.

ECOG performance status is used by researchers to assess how a participant's disease is progressing. The scores are: 0=Fully Active, able to carry out work without restrictions; 1=Restricted activity and able to carry out light work or sedentary nature; 2=capable of self-care but unable to carry out work activities; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely Disabled, and totally confined to bed or chair; 5=Dead. Change in ECOG performance status was defined as improved (less than the baseline value), no change (same as at baseline), worsened (greater than the baseline value) or missing (score is missing or was not recorded at baseline). If no measurement was recorded at Cycle 1 Day 1, the change was calculated in relation to the last recorded ECOG value prior to Day 1.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Number of participants with clinically significant changes in vital signs are reported. Vital sign parameters included body temperature, blood pressure, and pulse rate.

Number of participants with at least 2-grade change from baseline to worst toxicity grade in clinical laboratory parameters are reported. Laboratory parameters included hematology, clinical chemistry, and urinalysis.

KuDOS Pharmaceuticals Limited

AstraZeneca

Safety population included all participants who received at least one dose of study drug.

Participants received two 50 mg capsules in the morning and two 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion was met.

Olaparib 100 mg

Participants received eight 50 mg capsules in the morning and eight 50 mg capsules in the evening in 28-days cycle until confirmed disease progression, continuous treatment interruption, unacceptable toxicity or any other discontinuation criterion was met.

Olaparib 400 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The full analysis set comprised of all enrolled participants with positive BRCA status, who took at least one dose of investigational medicinal product irrespective of whether they completed the trial schedule and IMP regime or not.

The plasma concentration data was analysed using a population approach and polyadenosine 5' diphosphoribose polymerase (PARP) inhibition data had already been obtained from Study D0810C00002. Hence no pharmacokinetic and PARP inhibition data are included.

Global Clinical Lead

The per-protocol (PP) population included all enrolled participants who completed the trial schedule and medication regime without any major deviations to the protocol.

Confirmed Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

The PP population included all enrolled participants who completed the trial schedule and medication regime without any major deviations to the protocol.

Duration of Response (DoR) to Olaparib

Clinical Benefit Rate (CBR)

Best Percentage Change in Tumor Size

Progression-free Survival (PFS)

Cycle 7 Day 1

Withdrawal visit

Number of Participants With Improvement in Eastern Co-operative Oncology Group (ECOG) Performance Status Total Score From Baseline

Any TEAE

Any TESAE

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Tachycardia

Supraventricular arrhythmia

Number of Participants With Clinically Significant Changes in Vital Signs From Baseline

Hemoglobin

White blood cells

Absolute neutrophil count

Lymphocytes

Platelets

Activated partial thromboplastin time

Alanine aminotransferase

Aspartate aminotransferase

Alkaline phosphatase

Gamma glutamyl transferase

Albumin

Total bilirubin

Sodium (decrease)

Potassium (increase)

Creatinine

Glucose (increase)

Glucose (decrease)

Calcium (decrease)

Amylase

Lipase

Number of Participants With at Least 2-Grade Change From Baseline to Worst Toxicity Grade in Clinical Laboratory Parameters

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

KU-0059436 (AZD2281)(PARP inhibitor)

James Carmichael, BSc MBChB MD FRCP

The purpose of the study is to see if the drug KU 0059436 is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and for whom no curative therapeutic option exists.

Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer

A Phase II Open-label, Non-comparative, International, Multicentre Study to Assess the Efficacy and Safety of KU 0059436 Given Orally Twice Daily in Patients With Advanced BRCA1 or BRCA2 Associated Ovarian Cancer

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease from baseline in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Clinical Benefit (CB) is defined as the percentage of patients with a RECIST tumour response of confirmed complete response, partial response or stable disease for ≥8 weeks)

The best % change (reduction) from baseline in tumour size (defined as the sum of the longest diameters as measured among all target lesions).

Progression-Free Survival (PFS) is defined as the time from first dose to the earlier date of radiologic progression (as per RECIST criteria) or death by any cause in the absence of objective progression.

olaparib (KU-0059436; AZD2281) 100 mg oral capsules, twice daily

Olaparib 100 mg bd

olaparib (KU-0059436; AZD2281) 400 mg oral capsules, twice daily

Olaparib 400 mg bd

BRCA1 or BRCA2 mutations known to cause loss of gene function (clinical deleterious or suspected deleterious mutations).

BRCA mutation

Gerard Lynch

PP Analysis Set

ITT Analysis Set

PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm)

Confirmed Objective Tumour Response (According to Response Evaluation Criteria In Solid Tumors (RECIST)

Clinical Benefit (CB)

PP Analysis Set (includes all enrolled patients who complete the trial schedule and medication regime without any major deviations to the protocol - this is the main analysis population, with ITT used to confirm

Duration of Response

Best Percentage Change in Tumour Size

Progression-Free Survival (PFS)

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Anti-Bacterial Agents

Antibiotics, Antitubercular

AZD2281

Liposomal Doxorubicin

Jane Robertson, BSc, MBCHB, MD

Stan Kaye, BSc, MB, FRCP, FRCR, SMedSCi

The purpose of the study is to compare the efficacy and safety of 2 doses of drug AZD2281 against liposomal doxorubicin to see which is effective and well tolerated in treating patients with measurable BRCA1- or BRCA2-positive advanced ovarian cancer and who have failed previous platinum therapy.

Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer

A Phase II, Open-Label, Randomised, Comparative, International Multicentre Study to Assess the Safety and Efficacy of Different Doses of AZD2281 Given Orally Twice Daily Versus Intravenous Liposomal Doxorubicin Given Monthly in Patients With Advanced BRCA1- or BRCA2-Associated Ovarian Cancer Who Have Failed Previous Platinum-based Chemotherapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Novel Neoadjuvant and Adjuvant Strategy for Germline BRCA 1/2 Mutated Triple Negative Breast Cancer	NCT05485766	Triple Negative... Triple Negative... Breast Neoplasm... Breast Cancer BRCA1 Mutation BRCA2 Mutation BRCA Mutation BRCA-Associated...	Pembrolizumab Paclitaxel Carboplatin Olaparib Definitive Surg...	18 Years -	Okayama University
Nipple Delay Prior to Nipple Sparing Mastectomy: A Pilot RCT	NCT02526719	Breast Cancer	Nipple Delay su...	18 Years -	University Health Network, Toronto
Evaluation of Tomosynthesis for Characterization and the Management of Breast Lesions	NCT02959398	Breast Neoplasm... Tomosynthesis BRCA1 Protein BRCA2 Protein	Standard mammog... Standard mammog...	18 Years -	Assistance Publique - Hôpitaux de Paris
Study to Assess The Efficacy and Safety of a PARP Inhibitor For The Treatment of BRCA-positive Advanced Breast Cancer	NCT00494234	Breast Neoplasm...	Olaparib	18 Years - 130 Years	AstraZeneca
Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer	NCT00494442	Ovarian Neoplas...	KU-0059436 (AZD... KU-0059436 (AZD...	18 Years - 130 Years	AstraZeneca
Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer	NCT00628251	Ovarian Neoplas...	AZD2281 Liposomal Doxor... AZD2281	18 Years - 130 Years	AstraZeneca
Dose-finding Study Comparing Efficacy and Safety of a PARP Inhibitor Against Doxil in BRCA+ve Advanced Ovarian Cancer	NCT00628251	Ovarian Neoplas...	AZD2281 Liposomal Doxor... AZD2281	18 Years - 130 Years	AstraZeneca
A Study to Assess the Safety and Pharmacokinetics of an Inhibitor of Poly ADP-Ribose Polymerase-1 (PARP)	NCT00516373	Ovarian Neoplas... BRCA1 Protein BRCA2 Protein	KU-0059436 (AZD...	18 Years - 130 Years	AstraZeneca
The Potential for Oral Diindolylmethane (DIM) Supplementation to Increase the Production of the BRCA1 Protein in BRCA1 Mutation Carriers	NCT01022333	Breast Cancer	Diindolylmethan...	25 Years - 45 Years	Women's College Hospital
Study to Assess the Efficacy and Safety of a PARP Inhibitor for the Treatment of BRCA-positive Advanced Ovarian Cancer	NCT00494442	Ovarian Neoplas...	KU-0059436 (AZD... KU-0059436 (AZD...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for brca1 protein